1. Alteration of Runt-related Transcription Factor 3 Gene Expression and Biologic Behavior of Esophageal Carcinoma TE-1 Cells after 5-Azacytidine Intervention
- Author
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Hong Liu, Zhou Wang, Hua-Xia Chen, Shuai Wang, and Javed Akhtar
- Subjects
Male ,Antimetabolites, Antineoplastic ,Cancer Research ,Esophageal Neoplasms ,Epidemiology ,Blotting, Western ,Mice, Nude ,Biology ,law.invention ,Mice ,Cell Movement ,law ,Gene expression ,Cell Adhesion ,Tumor Cells, Cultured ,Carcinoma ,medicine ,Animals ,Humans ,Neoplasm Invasiveness ,Promoter Regions, Genetic ,Gene ,Transcription factor ,Cell Proliferation ,Demethylation ,Mice, Inbred BALB C ,Messenger RNA ,Reverse Transcriptase Polymerase Chain Reaction ,Runt ,Public Health, Environmental and Occupational Health ,DNA, Neoplasm ,DNA Methylation ,medicine.disease ,Xenograft Model Antitumor Assays ,digestive system diseases ,Gene Expression Regulation, Neoplastic ,Core Binding Factor Alpha 3 Subunit ,Oncology ,Azacitidine ,Carcinoma, Squamous Cell ,Cancer research ,Suppressor ,Female - Abstract
5-Azacytidine (5-azaC) was originally identified as an anticancer drug (NSC102876) which can cause hypomethylation of tumor suppressor genes. To assess its effects on runt-related transcription factor 3 (RUNX3), expression levels and the promoter methylation status of the RUNX3 gene were assessed. We also investigated alteration of biologic behavior of esophageal carcinoma TE-1 cells. MTT assays showed 5-azaC inhibited the proliferation of TE-1 cells in a time and dose-dependent way. Although other genes could be demethylated after 5-azaC intervention, we focused on RUNX3 gene in this study. The expression level of RUNX3 mRNA increased significantly in TE-1 cells after treatment with 5-azaC at hypotoxic levels. RT-PCR showed 5-azaC at 50 μM had the highest RUNX3-induction activity. Methylation-specific PCR indicated that 5-azaC induced RUNX3 expression through demethylation. Migration and invasion of TE-1 cells were inhibited by 5-azaC, along with growth of Eca109 xenografts in nude mice. In conclusion, we demonstrate that the RUNX3 gene can be reactivated by the demethylation reagent 5-azaC, which inhibits the proliferation, migration and invasion of esophageal carcinoma TE-1 cells.
- Published
- 2013